头围和Apoe E4 基因与阿尔茨海默病有关
WESTPORT, CT (Reuters Health) - A smaller head circumference coupled with the apolipoprotein E e4 (APOE e4) gene appears to hasten the onset of Alzheimer's disease (AD), according to a report published in the October 23rd issue of Neurology.
The current findings lend support to the "brain reserve" theory of AD, the authors suggest. Neuropathologic lesions accumulate in the brain and once a critical "brain reserve" threshold is violated, cognitive function is compromised. A smaller head circumference, indicative of reduced brain reserve, would result in a mean earlier clinical onset of AD once lesions start to occur.
Dr. A. Borenstein Graves from the University of South Florida in Tampa and colleagues followed 1869 nondemented subjects, 65 years of age and older, for a mean of 3.8 years to determine the incidence of AD. The head circumference of all subjects was measured at baseline. APOE status was available for 1111 of the subjects.
Fifty-nine incident cases of probable AD were identified, the authors note. Individuals with the APOE e4 gene were 4.8 times more likely to develop AD than subjects without this gene. Individuals with head circumferences less than 21.4 inches and the APOE e4 gene were 14.1 times more likely to develop AD. Head circumference alone was not significantly associated with an increased risk of AD.
People who developed AD were also older, less educated, shorter, lighter, and had lower estimated verbal IQ scores than people who did not develop AD, the authors note.
"We don't think that head circumference is a risk factor for the pathology of AD," Dr. Graves told Reuters Health. "However, head circumference does seem to influence the age of clinical onset in individuals with pathologic changes," she said.
"Therefore, in people with APOE e4, a gene associated with rapid plaque accumulation, clinical disease onset is earlier in individuals with smaller head circumferences."
Dr. Graves mentioned that her team is "currently trying to understand why some people with the neuropathologic changes of AD do not develop clinical manifestations in their lifetime."
Once the factors that influence disease onset are understood, "we may be able to develop therapeutic interventions that delay onset so that predisposed individuals actually die from other causes before AD is clinically apparent," she said.
Neurology 2001;57:1453-1460.
-Westport Newsroom 203 319 2700, http://www.100md.com
The current findings lend support to the "brain reserve" theory of AD, the authors suggest. Neuropathologic lesions accumulate in the brain and once a critical "brain reserve" threshold is violated, cognitive function is compromised. A smaller head circumference, indicative of reduced brain reserve, would result in a mean earlier clinical onset of AD once lesions start to occur.
Dr. A. Borenstein Graves from the University of South Florida in Tampa and colleagues followed 1869 nondemented subjects, 65 years of age and older, for a mean of 3.8 years to determine the incidence of AD. The head circumference of all subjects was measured at baseline. APOE status was available for 1111 of the subjects.
Fifty-nine incident cases of probable AD were identified, the authors note. Individuals with the APOE e4 gene were 4.8 times more likely to develop AD than subjects without this gene. Individuals with head circumferences less than 21.4 inches and the APOE e4 gene were 14.1 times more likely to develop AD. Head circumference alone was not significantly associated with an increased risk of AD.
People who developed AD were also older, less educated, shorter, lighter, and had lower estimated verbal IQ scores than people who did not develop AD, the authors note.
"We don't think that head circumference is a risk factor for the pathology of AD," Dr. Graves told Reuters Health. "However, head circumference does seem to influence the age of clinical onset in individuals with pathologic changes," she said.
"Therefore, in people with APOE e4, a gene associated with rapid plaque accumulation, clinical disease onset is earlier in individuals with smaller head circumferences."
Dr. Graves mentioned that her team is "currently trying to understand why some people with the neuropathologic changes of AD do not develop clinical manifestations in their lifetime."
Once the factors that influence disease onset are understood, "we may be able to develop therapeutic interventions that delay onset so that predisposed individuals actually die from other causes before AD is clinically apparent," she said.
Neurology 2001;57:1453-1460.
-Westport Newsroom 203 319 2700, http://www.100md.com